Inflammatory Bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is comprised predominantly of Crohn's disease and ulcerative colitis. Both of these are debilitating inflammatory diseases characterized by inflammation of the digestive tract accompanied by severe diarrhea and abdominal pain leading to life-threatening complications. Crohn's disease involves inflammation of all layers of the bowel wall and any part of the gastrointestinal tract; with the most common sites being the small intestine, colon, and stomach. In contrast, ulcerative colitis is characterized by chronic inflammation of the colon but does not involve the small intestine. Currently, invasive procedures are used to confirm a diagnosis of IBD. These procedures involve endoscopy and clinical history. In order to obtain quantitative information on disease activity (as opposed to relying on subjective patient measurements) and to avoid invasive imaging procedures, there has been an active effort to identify serum/plasma microvesicle biomarkers that are indicative of disease subtype and inflammatory activity.
Pathogenesis of IBD involves interactions between both the innate and the adaptive immune system. Recent evidence suggests that these inflammatory systems can be influenced by both immune and non-immune cells. Platelets are non-immune, anuclear cells that affect blood hemostatis. Platelets also play an active role in a variety of inflammatory processes and platelet activation has been associated with chronic inflammatory coronary syndromes and autoimmune disease such as rheumatoid arthritis and systemic lupus erythematosus. Increased numbers of platelets have been seen in both Crohn's disease and ulcerative colitis. Upon activation, these platelets secrete pro-inflammatory cytokines that activate the same cellular and molecular pathways utilized by immune cells participating in an IDB episode. For instance, activated platelets release the potent chemokine RANTES, which is retained by endothelial cells and used to mediate adhesion of T cells to these cells. This cascade provides a link between platelet activation and T cell recruitment in IBD and suggests that platelets are involved in the cell-mediated enteric immune response.
microRNAs (miRNAs) are small, highly conserved non-coding RNAs that are thought to have a regulatory effect in a wide variety of eukaryotic organisms, including humans, plants and insects. Currently over 1000 mature miRNAs have been characterized in humans and it is believed that approximately 30% of all annotated human genes may potentially be targeted by miRNAs through post-transcriptional mechanisms including mRNA cleavage, inhibition of translation initiation, mRNA de-adenylation and/or sequestration of mRNA into P-bodies. miRNAs have been shown to play an integral role in immune response, cellular proliferation, apoptosis, metabolism, viral replication, stem cell differentiation and human development and are involved in the pathophysiology of autoimmune diseases and numerous cancers.
There is a significant need for identification of differentially expressed blood-based inflammatory biomarkers (or modulators of these inflammatory markers) that can be used for non-invasive diagnosis and therapeutic management of IBD. The present invention meets this need.